Carotid Artery Calcification
Lipid-filled plaques are more of a concern.
It is well known that carotid artery atherosclerosis predisposes a patient to embolic events. It is unclear, however, whether a correlation exists between carotid plaque calcification and patient outcome.
For the past 150 years, medical experts have recognized that dystrophic calcification (calcification of normal tissue) is a common component of the atherosclerotic lesion. The cause of the calcification is unclear, although an apoptotic mechanism resulting in cell death is thought to contribute to dystrophic calcification. Lamellar bone (ossification) can also develop in both arteries and cardiac valves.
Calcification in the Carotid Artery
There is no question that calcification in the carotid artery is undesirable; its very existence indicates that the patient has atheroma, which may result in both ischemia and a cerebrovascular event. The question arises whether the presence of bone and extensive sheets of calcification in the carotid artery are protective from embolic events, or whether those conditions are associated with a higher frequency of stroke and transient ischemic attacks (TIA).
Hunt et al recently evaluated carotid endarterectomy plaques for lamellar bone formation, dystrophic calcification and inflammation.1 These investigators found that stroke and TIA occurred less frequently in patients who had plaques with large calcific granules. The presence of lamellar bone, which directly correlated with the presence of sheet-like calcifications, was inversely correlated with ulcerated lesions. These results indicate that bone formation tends to occur in heavily calcified carotid lesions devoid of ulceration or hemorrhages. Therefore, patients with extensive calcification of carotid plaques are less likely to have symptomatic disease than those with lipid-filled plaques.
Calcification and Vascular Disease
Although there are no published studies correlating the presence of bone and vascular events, there are published clinical studies evaluating the relationship between calcification and symptoms of vascular disease. Johnson et al reported that “soft” plaques, noted on ultrasound, have a greater tendency toward subintimal hemorrhage, ulceration, or primary embolization than more well-organized plaques.2 Investigators from the TROMSO Study in Norway used high-resolution ultrasound B-mode imaging and found that echolucent plaques (plaques with a higher content of lipid and hemorrhage) were associated with a higher risk of neurologic events than were echorich plaques that strongly reflect the echo signal.3 Echorich plaques typically contain more calcification and fibrosis than echolucent plaques. In another Scandinavian study, Gronholdt et al found that echolucent plaques that caused stenosis >50% in diameter as measured by Doppler ultrasound are associated with a risk of future stroke in symptomatic, but not asymptomatic, individuals.4-5 Cohen et al used transesophageal echocardiography at the time of stroke and found that the highest relative risk for vascular events was among patients with non-calcified plaques.6
The majority of the published literature indicates that dystrophic calcification and possibly bone formation do not increase the risk of stroke, but rather may be a stabilizing influence conferring protection from embolic events. Further studies are needed to investigate the relationship between carotid calcification and stroke, as well as the impact of pharmacologic therapy on this process.
Emile R. Mohler III, MD is Director of Vascular Medicine at University of Pennsylvania Health System, Philadelphia, Pennsylvania. Dr. Mohler may be reached at email@example.com.
Material extracted from Dr. Mohler’s presentation at SVMB’s annual meeting, delivered on June 7, 2002, in Boston, Massachusetts.
1. Hunt JL, Fairman R, Mitchell ME, et al. Bone formation in carotid plaques: A clinicopathologic study. Stroke. 2002.
2. Johnson JM, Kennelly MM, Decesare D, et al. Natural history of asymptomatic carotid plaque. Arch Surg. 1985;120(9):1010-1012.
3. Mathiesen EB, Bonaa KH, Joakimsen O. Echolucent plaques are associated with high risk of ischemic cerebrovascular events in carotid stenosis: The TROMSO study. Circulation. 2001;103(17):2171-2175.
4. Gronholdt ML, Wiebe BM, Laursen H, et al. Lipid-rich carotid artery plaques appear echolucent on ultrasound B-mode images and may be associated with intraplaque hemorrhage. Euro 1 Vasc & Endovasc Surg. 1997;14:439-445.
5. Gronholdt ML, Nordestgaard BG, Schroeder TV, et al. Ultrasonic echolucent carotid plaques predict future strokes. Circulation. 2001;104(1):68-73.
6. Cohen A, Tzourio C, Bertrand B, et al. Aortic plaque morphology and vascular events: A follow-up study in patients with ischemic stroke. FAPS Investigators. French Study of Aortic Plaques in Stroke. Circulation. 1997;96(11):3838-3841.